1. Field of the Invention
The present invention relates to a mass spectrometer and a method of mass spectrometry.
2. Discussion of the Prior Art
The present invention relates to a mass spectrometer and to a method of mass spectrometry.
Radio Frequency (RF) ion guides are commonly used for confining and transporting ions and comprise an arrangement of electrodes wherein an RF voltage is applied between neighbouring electrodes so that a pseudo-potential well or valley is provided. The pseudo-potential well can be arranged to confine ions and may be used to transport ions by acting as an ion guide. Its use as an ion guide is well known and can be very efficient.
Known RF ion guides can still function efficiently as an ion guide even at relatively high pressures where ions are likely to undergo frequent collisions with residual gas molecules. The collisions with gas molecules may cause ions to scatter and lose energy but the pseudo-potential well generated by the RF ion guide acts to radially confine the ions within the ion guide. In this respect the known RF ion guide has an advantage over guide wire types of ion guides where a DC voltage is applied to a central wire running down the centre of a conducting tube and wherein ions are held in orbit around the central guide wire. If ions undergo many collisions with gas molecules in a guide wire type of ion guide then they will lose energy and will eventually collapse into the central guide wire and be lost.
It is desired to provide an improved ion guide for a mass spectrometer and an improved method of mass spectrometry.
According to an aspect of the present invention there is provided a mass spectrometer comprising:
a device for temporally or spatially dispersing a group of ions according to a physico-chemical property;
an ion guide comprising a plurality of electrodes, the ion guide receiving in use at least some of the ions which have become dispersed according to the physico-chemical property;
wherein multiple trapping regions are generated or created along at least a portion of the length of the ion guide wherein at least a first group of ions having a physico-chemical property within a first range are trapped within a first trapping region and a second group of ions having a physico-chemical property within a second different range are trapped within a second different trapping region and wherein the multiple trapping regions are translated along at least a portion of the length of the ion guide.
According to the preferred embodiment at least a majority of ions trapped within the first trapping region and/or at least a majority of ions trapped within the second trapping region have substantially the same or similar the physico-chemical property. For example, at least 50%, 60%, 70%, 80%, 90% or 95% of ions in a particular trapping region may have substantially the same or similar physico-chemical property.
The physico-chemical property is preferably mass to charge ratio. Ions may be separated according to their mass to charge ratio by providing a field free region arranged upstream of the ion guide wherein ions which have been accelerated to have substantially the same kinetic energy become dispersed according to their mass to charge ratio. The field free region may be provided within an ion guide selected from the group consisting of: (i) a quadrupole rod set; (ii) a hexapole rod set; (iii) an octopole or higher order rod set; (iv) an ion tunnel ion guide comprising a plurality of electrodes having apertures through which ions are transmitted, the apertures being substantially the same size; (v) an ion funnel ion guide comprising a plurality of electrodes having apertures through which ions are transmitted, the apertures becoming progressively smaller or larger; and (vi) a segmented rod set.
According to the preferred embodiment a pulsed ion source is provided wherein in use a packet or ions emitted by the pulsed ion source enters the field free region. According to another embodiment an ion trap may be arranged upstream of the field free region wherein in use the ion trap releases a packet of ions which enters the field free region.
According to a less preferred embodiment the physico-chemical property may be ion mobility. According to this embodiment a drift region may be arranged upstream of the ion trap wherein ions become dispersed according to their ion mobility. In such an embodiment the drift region preferably has a constant axial electric field or a time varying axial electric field. The drift region may be provided within an ion guide selected from the group consisting of: (i) a quadrupole rod set; (ii) a hexapole rod set; (iii) an octopole or higher order rod set; (iv) an ion tunnel ion guide comprising a plurality of electrodes having apertures through which ions are transmitted, the apertures being substantially the same size; (v) an ion funnel ion guide comprising a plurality of electrodes having apertures through which ions are transmitted, the apertures becoming progressively smaller or larger; and (vi) a segmented rod set.
A pulsed ion source may be provided wherein in use a packet of ions emitted by the pulsed ion source enters the drift region. An ion trap may be arranged upstream of the drift region wherein in use the ion trap releases a packet of ions which enters the drift region.
According to another aspect of the present invention there is provided a mass spectrometer comprising:
a mass to charge ratio selective ion trap which releases in use at least a first group of ions having mass to charge ratios within a first range and then at least a second group of ions having mass to charge ratios within a second range;
an ion guide comprising a plurality of electrodes arranged to receive at least some of the first group of ions and at least some of the second group of ions;
wherein multiple trapping regions are generated or created along at least a portion of the length of the ion guide wherein at least some of the ions of the first group are trapped within a first trapping region and at least some of the ions of the second group are trapped within a second different trapping region; and
wherein the multiple trapping regions are translated along at least a portion of the length of the ion guide.
The mass to charge ratio selective ion trap may comprise a 2D (linear) quadrupole ion trap, a 3D (Paul) quadrupole ion trap or a Penning ion trap.
Preferably, at least a majority of the ions trapped within the first trapping region have substantially the same mass to charge ratio and/or at least a majority of the ions trapped within the second trapping region have substantially the same mass to charge ratio.
Preferably, at least a majority of the ions trapped within the first trapping region have mass to charge ratios which differ by less than x mass to charge ratio units and/or at least a majority of the ions trapped within the second trapping region have mass to charge ratios which differ by less than x mass to charge ratio units, wherein x is selected from the group consisting of: (i) 500; (ii) 450; (iii) 400; (iv) 350; (v) 300; (vi) 250; (vii) 200; (viii) 150; (ix) 100; (x) 90; (xi) 80; (xii) 70; (xiii) 60; (xiv) 50; (xv) 40; (xvi) 30; (xvii) 20; (xviii) 10; and (xix) 5.
At least a majority of the ions trapped within the first trapping region and/or at least a majority of the ions trapped within the second trapping region may have mass to charge ratios which differ by less than: (i) 30%; (ii) 25%; (iii) 20%; (iv) 15%; (v) 10%; (vi) 5%; (vii) 4%; (viii) 3%; (ix) 2%; or (x) 1%.
According to the preferred embodiment one or more transient DC voltages or one or more transient DC voltage waveforms are progressively applied to the electrodes so that ions are urged along the ion guide.
An axial voltage gradient may be maintained along at least a portion of the length of the ion guide and the axial voltage gradient preferably varies with time whilst ions are being transmitted through the ion guide.
The ion guide preferably comprises a first electrode held at a first reference potential, a second electrode held at a second reference potential, and a third electrode held at a third reference potential, wherein:
at a first time t1 a first DC voltage is supplied to the first electrode so that the first electrode is held at a first potential above or below the first reference potential;
at a second later time t2 a second DC voltage is supplied to the second electrode so that the second electrode is held at a second potential above or below the second reference potential; and
at a third later time t3 a third DC voltage is supplied to the third electrode so that the third electrode is held at a third potential above or below the third reference potential.
According to one embodiment, at the first time t1 the second electrode is at the second reference potential and the third electrode is at the third reference potential;
at the second time t2 the first electrode is at the first potential and the third electrode is at the third reference potential; and
at the third time t3 the first electrode is at the first potential and the second electrode is at the second potential.
According to another embodiment at the first time t1 the second electrode is at the second reference potential and the third electrode is at the third reference potential;
at the second time t2 the first electrode is no longer supplied with the first DC voltage so that the first electrode is returned to the first reference potential and the third electrode is at the third reference potential; and
at the third time t3 the first electrode is at the first reference potential and the second electrode is no longer supplied with the second DC voltage so that the second electrode is returned to the second reference potential.
Preferably, the first, second and third reference potentials are substantially the same. The first, second and third DC voltages are also preferably substantially the same. Preferably, the first, second and third potentials are substantially the same.
According to an embodiment the ion guide comprises 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or  greater than 30 segments, wherein each segment comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or  greater than 30 electrodes and wherein the electrodes in a segment are maintained at substantially the same DC potential. Preferably, a plurality of segments are maintained at substantially the same DC potential. Preferably, each segment is maintained at substantially the same DC potential as the subsequent nth segment wherein n is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or  greater than 30.
Ions are preferably confined radially within the ion guide by an AC or RF electric field. Ions are preferably radially confined within the ion guide in a pseudo-potential well and are constrained axially by a real potential barrier or well.
The transit time of ions through the ion guide is selected from the group consisting of: (i) less than or equal to 20 ms; (ii) less than or equal to 10 ms; (iii) less than or equal to 5 ms; (iv) less than or equal to 1 ms; and (v) less than or equal to 0.5 ms.
The ion guide and/or the drift region are preferably maintained, in use, at a pressure selected from the group consisting of: (i) greater than or equal to 0.0001 mbar; (ii) greater than or equal to 0.0005 mbar; (iii) greater than or equal to 0.001 mbar; (iv) greater than or equal to 0.005 mbar; (v) greater than or equal to 0.01 mbar; (vi) greater than or equal to 0.05 mbar; (vii) greater than or equal to 0.1 mbar; (viii) greater than or equal to 0.5 mbar; (ix) greater than or equal to 1 mbar; (x) greater than or equal to 5 mbar; and (xi) greater than or equal to 10 mbar.
The ion guide and/or the drift region are preferably maintained, in use, at a pressure selected from the group consisting of: (i) less than or equal to 10 mbar; (ii) less than or equal to 5 mbar; (iii) less than or equal to 1 mbar; (iv) less than or equal to 0.5 mbar; (v) less than or equal to 0.1 mbar; (vi) less than or equal to 0.05 mbar; (vii) less than or equal to 0.01 mbar; (viii) less than or equal to 0.005 mbar; (ix) less than or equal to 0.001 mbar; (x) less than or equal to 0.0005 mbar; and (xi) less than or equal to 0.0001 mbar.
The ion guide and/or the drift region are preferably maintained, in use, at a pressure selected from the group consisting of: (i) between 0.0001 and 10 mbar; (ii) between 0.001 and 1 mbar; (iii) between 0.0001 and 0.1 mbar; (iv) between 0.0001 and 0.01 mbar; (v) between 0.0001 and 0.001 mbar; (vi) between 0.001 and 10 mbar; (vii) between 0.001 and 1 mbar; (viii) between 0.001 and 0.1 mbar; (ix) between 0.001 and 0.01 mbar; (x) between 0.01 and 10 mbar; (xi) between 0.01 and 1 mbar; (xii) between 0.01 and 0.1 mbar; (xiii) between 0.1 and 10 mbar; (xiv) between 0.1 and 1 mbar; and (xv) between 1 and 10 mbar.
The field free region is preferably maintained, in use, at a pressure selected from the group consisting of: (i) greater than or equal to 1xc3x9710xe2x88x927 mbar; (ii) greater than or equal to 5xc3x9710xe2x88x927 mbar; (iii) greater than or equal to 1xc3x9710xe2x88x926 mbar; (iv) greater than or equal to 5xc3x9710xe2x88x926 mbar; (v) greater than or equal to 1xc3x9710xe2x88x925 mbar; and (vi) greater than or equal to 5xc3x9710xe2x88x925 mbar.
The field free region is preferably maintained, in use, at a pressure selected from the group consisting of; (i) less than or equal to 1xc3x9710xe2x88x924 mbar; (ii) less than or equal to 5xc3x9710xe2x88x925 mbar; (iii) less than or equal to 1xc3x9710xe2x88x925 mbar; (iv) less than or equal to 5xc3x9710xe2x88x926 mbar; (v) less than or equal to 1xc3x9710xe2x88x926 mbar; (vi) less than or equal to 5xc3x9710xe2x88x927 mbar; and (vii) less than or equal to 1xc3x9710xe2x88x927 mbar.
The field free region is preferably maintained, in use, at a pressure selected from the group consisting of: (i) between 1xc3x9710xe2x88x927 and 1xc3x9710xe2x88x924 mbar; (ii) between 1xc3x9710xe2x88x927 and 5xc3x9710xe2x88x925 mbar; (iii) between 1xc3x9710xe2x88x927 and 1xc3x9710xe2x88x925 mbar; (iv) between 1xc3x9710xe2x88x927 and 5xc3x9710xe2x88x926 mbar; (v) between 1xc3x9710xe2x88x927 and 1xc3x9710xe2x88x926 mbar; (vi) between 1xc3x9710xe2x88x927 and 5xc3x9710xe2x88x927 mbar; (vii) between 5xc3x9710xe2x88x927 and 1xc3x9710xe2x88x924 mbar; (viii) between 5xc3x9710xe2x88x927 and 5xc3x9710xe2x88x925 mbar; (ix) between 5xc3x9710xe2x88x927 and 1xc3x9710xe2x88x925 mbar; (x) between 5xc3x9710xe2x88x927 and 5xc3x9710xe2x88x926 mbar; (xi) between 5xc3x9710xe2x88x927 and 1xc3x9710xe2x88x926 mbar; (xii) between 1xc3x9710xe2x88x926 mbar and 1xc3x9710xe2x88x924 mbar; (xiii) between 1xc3x9710xe2x88x926 and 5xc3x9710xe2x88x925 mbar; (xiv) between 1xc3x9710xe2x88x926 and 1xc3x9710xe2x88x925 mbar; (xv) between 1xc3x9710xe2x88x926 and 5xc3x9710xe2x88x926 mbar; (xvi) between 5xc3x9710xe2x88x926 mbar and 1xc3x9710xe2x88x924 mbar; (xvii) between 5xc3x9710xe2x88x926 and 5xc3x9710xe2x88x925 mbar; (xviii) between 5xc3x9710xe2x88x926 and 1xc3x9710xe2x88x925 mbar; (xix) between 1xc3x9710xe2x88x925 mbar and 1xc3x9710xe2x88x924 mbar; (xx) between 1xc3x9710xe2x88x925 and 5xc3x9710xe2x88x925 mbar; (xxi) between 5xc3x9710xe2x88x925 and 1xc3x9710xe2x88x924 mbar.
The ion guide and/or the drift region are preferably maintained, in use, at a pressure such that a viscous drag is imposed upon ions passing through the ion guide and/or the drift region.
According to the preferred embodiment one or more transient DC voltages or one or more transient DC voltage waveforms are initially provided at a first axial position and are then subsequently provided at second, then third different axial positions along the ion guide.
One or more transient DC voltages or one or more transient DC voltage waveforms preferably move in use from one end of the ion guide to another end of the ion guide so that ions are urged along the ion guide.
The one or more transient DC voltages preferably create: (i) a potential hill or barrier; (ii) a potential well; (iii) multiple potential hills or barriers; (iv) multiple potential wells; (v) a combination of a potential hill or barrier and a potential well; or (vi) a combination of multiple potential hills or barriers and multiple potential wells.
The one or more transient DC voltage waveforms preferably comprise a repeating waveform such as a square wave.
The amplitude of the one or more transient DC voltages or the one or more transient DC voltage waveforms may remain substantially constant with time. Alternatively, the amplitude of the one or more transient DC voltages or the one or more transient DC voltage waveforms may vary with time. The amplitude of the one or more transient DC voltages or the one or more transient DC voltage waveforms may either: (i) increases with time; (ii) increases then decreases with time; (iii) decreases with time; or (iv) decreases then increases with time.
According to an embodiment the ion guide comprises an upstream entrance region, a downstream exit region and an intermediate region, wherein:
in the entrance region the amplitude of the one or more transient DC voltages or the one or more transient DC voltage waveforms has a first amplitude;
in the intermediate region the amplitude of the one or more transient DC voltages or the one or more transient DC voltage waveforms has a second amplitude; and
in the exit region the amplitude of the one or more transient DC voltages or the one or more transient DC voltage waveforms has a third amplitude.
The entrance and/or exit region preferably comprise a proportion of the total axial length of the ion guide selected from the group consisting of: (i) less than 5%; (ii) 5-10%; (iii) 10-15%; (iv) 15-20%; (v) 20-25%; (vi) 25-30%; (vii) 30-35%; (viii) 35-40%; and (ix) 40-45%.
The first and/or third amplitudes are preferably substantially zero and the second amplitude is preferably substantially non-zero.
The second amplitude is preferably larger than the first amplitude and/or the second amplitude is preferably larger than the third amplitude.
One or more transient DC voltages or one or more transient DC voltage waveforms preferably pass in use along the ion guide with a first velocity. The first velocity preferably: (i) remains substantially constant; (ii) varies; (iii) increases; (iv) increases then decreases; (v) decreases; (vi) decreases then increases; (vii) reduces to substantially zero; (viii) reverses direction; or (ix) reduces to substantially zero and then reverses direction.
The one or more transient DC voltages or the one or more transient DC voltage waveforms preferably cause ions within the ion guide to pass along the ion guide with a second velocity.
The difference between the first velocity and the second velocity is preferably less than or equal to 100 m/s, 90 m/s, 80 m/s, 70 m/s, 60 m/s, 50 m/s, 40 m/s, 30 m/s, 20 m/s, 10 m/s, 5 m/s or 1 m/s.
The first velocity is preferably selected from the group consisting of; (i) 10-250 m/s; (ii) 250-500 m/s; (iii) 500-750 m/s; (iv) 750-1000 m/s; (v) 1000-1250 m/s; (vi) 1250-1500 m/s; (vii) 1500-1750 m/s; (viii) 1750-2000 m/s; (ix) 2000-2250 m/s; (x) 2250-2500 m/s; (xi) 2500-2750 m/s; and (xii) 2750-3000 m/s.
The second velocity is preferably selected from the group consisting of: (i) 10-250 m/s; (ii) 250-500 m/s; (iii) 500-750 m/s; (iv) 750-1000 m/s; (v) 1000-1250 m/s; (vi) 1250-1500 m/s; (vii) 1500-1750 m/s; (viii) 1750-2000 m/s; (ix) 2000-2250 m/s; (x) 2250-2500 m/s; (xi) 2500-2750 m/s; and (xii) 2750-3000 m/s.
According to the preferred embodiment the second velocity is substantially the same as the first velocity.
The one or more transient DC voltages or the one or more transient DC voltage waveforms preferably have a frequency, and wherein the frequency: (i) remains substantially constant; (ii) varies; (iii) increases; (iv) increases then decreases; (v) decreases; or (vi) decreases then increases.
The one or more transient DC voltages or the one or more transient DC voltage waveforms preferably have a wavelength, and wherein the wavelength: (i) remains substantially constant; (ii) varies; (iii) increases; (iv) increases then decreases; (v) decreases; or (vi) decreases then increases.
According to an embodiment two or more transient DC voltages or two or more transient DC voltage waveforms are arranged to move: (i) in the same direction; (ii) in opposite directions; (iii) towards each other; or (iv) away from each other.
The one or more transient DC voltages or the one or more transient DC voltage waveforms are preferably repeatedly generated and passed in use along the ion guide, and wherein the frequency of generating the one or more transient DC voltages or the one or more transient DC voltage waveforms: (i) remains substantially constant; (ii) varies; (iii) increases; (iv) increases then decreases; (v) decreases; or (vi) decreases then increases.
Preferably, the one or more transient DC voltages or the one or more transient DC voltage waveforms has a wavelength which remains substantially the same and a frequency which decreases with time so that the velocity of the one or more transient DC voltages or the one or more transient DC voltages decreases with time.
Pulses of ions preferably emerge from an exit of the ion guide.
The mass spectrometer preferably further comprises an ion detector, the ion detector being arranged to be substantially phase locked in use with the pulses of ions emerging from the exit of the ion guide.
The mass spectrometer preferably further comprises a Time of Flight mass analyser comprising an electrode for injecting ions into a drift region, the electrode being arranged to be energised in use in a substantially synchronised manner with the pulses of ions emerging from the exit of the ion guide.
Preferably, the mass spectrometer further comprises an ion trap arranged downstream of the ion guide, the ion trap being arranged to store and/or release ions from the ion trap in a substantially synchronised manner with the pulses of ions emerging from the exit of the ion guide. The mass spectrometer may also comprise an mass filter arranged downstream of the ion guide, wherein a mass to charge ratio transmission window of the mass filter is varied in a substantially synchronised manner with the pulses of ions emerging from the exit of the ion guide.
The ion guide may comprise an ion funnel comprising a plurality of electrodes having apertures therein through which ions are transmitted, wherein the diameter of the apertures becomes progressively smaller or larger. Alternatively, the ion guide may comprise an ion tunnel comprising a plurality of electrodes having apertures therein through which ions are transmitted, wherein the diameter of the apertures remains substantially constant. The ion guide may comprise a stack of plate, ring or wire loop electrodes.
The ion guide preferably comprises a plurality of electrodes, each electrode having an aperture through which ions are transmitted in use. Each electrode preferably has a substantially circular aperture. Preferably, each electrode has a single aperture through which ions are transmitted in use.
The diameter of the apertures of at least 50%, 60%, 70%, 80%, 90% or 95% of the electrodes forming the ion guide is preferably selected from the group consisting of: (i) less than or equal to 10 mm; (ii) less than or equal to 9 mm; (iii) less than or equal to 8 mm; (iv) less than or equal to 7 mm; (v) less than or equal to 6 mm; (vi) less than or equal to 5 mm; (vii) less than or equal to 4 mm; (viii) less than or equal to 3 mm; (ix) less than or equal to 2 mm; and (x) less than or equal to 1 mm.
Preferably, at least 50%, 60%, 70%, 80%, 90% or 95% of the electrodes forming the ion guide have apertures which are substantially the same size or area.
According to a less preferred embodiment the ion guide may comprise a segmented rod set.
The ion guide may consist of: (i) 10-20 electrodes; (ii) 20-30 electrodes; (iii) 30-40 electrodes; (iv) 40-50 electrodes; (v) 50-60 electrodes; (vi) 60-70 electrodes; (vii) 70-80 electrodes; (viii) 80-90 electrodes; (ix) 90-100 electrodes; (x) 100-110 electrodes; (xi) 110-120 electrodes; (xii) 120-130 electrodes; (xiii) 130-140 electrodes; (xiv) 140-150 electrodes; or (xv) more than 150 electrodes.
The thickness of at least 50%, 60%, 70%, 80%, 90% or 95% of the electrodes may be selected from the group consisting of: (i) less than or equal to 3 mm; (ii) less than or equal to 2.5 mm; (iii) less than or equal to 2.0 mm; (iv) less than or equal to 1.5 mm; (v) less than or equal to 1.0 mm; and (vi) less than or equal to 0.5 mm.
The ion guide preferably has a length selected from the group consisting of: (i) less than 5 cm; (ii) 5-10 cm; (iii) 10-15 cm; (iv) 15-20 cm; (v) 20-25 cm; (vi) 25-30 cm; and (vii) greater than 30 cm.
Preferably, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of the electrodes are connected to both a DC and an AC or RF voltage supply. Preferably, axially adjacent electrodes are supplied with AC or RF voltages having a phase difference of 180xc2x0.
The mass spectrometer preferably further comprises an ion source selected from the group consisting of: (i) Electrospray (xe2x80x9cESIxe2x80x9d) ion source; (ii) Atmospheric Pressure Chemical Ionisation (xe2x80x9cAPCIxe2x80x9d) ion source; (iii) Atmospheric Pressure Photo Ionisation (xe2x80x9cAPPIxe2x80x9d) ion source; (iv) Matrix Assisted Laser Desorption Ionisation (xe2x80x9cMALDIxe2x80x9d) ion source; (v) Laser Desorption Ionisation (xe2x80x9cLDIxe2x80x9d) ion source; (vi) Inductively Coupled Plasma (xe2x80x9cICPxe2x80x9d) ion source; (vii) Electron Impact (xe2x80x9cEIxe2x80x9d) ion source; (viii) Chemical Ionisation (xe2x80x9cCIxe2x80x9d) ion source; (ix) a Fast Atom Bombardment (xe2x80x9cFABxe2x80x9d) ion source; and (x) a Liquid Secondary Ions Mass Spectrometry (xe2x80x9cLSIMSxe2x80x9d) ion source.
The ion source may comprise a continuous ion source or a pulsed ion source.
According to the preferred embodiment ions exiting the ion guide are arranged to have substantially constant energy substantially independent of their mass to charge ratio.
Preferably, a DC potential waveform is applied to the electrodes and wherein the velocity of the DC potential waveform becomes progressively slower. The ions in a pulse of ions emitted from the ion guide preferably have substantially the same energy or similar energies. Preferably, the ions from a plurality of pulses of ions emitted from the ion guide have substantially the same energy or similar energies.
A mass analyser is preferably provided to mass analyse the ions exiting the ion guide. The ions exiting the ion guide are preferably accelerated through a constant voltage difference prior to mass analysing the ions. The ions are preferably mass analysed by an orthogonal acceleration Time of Flight mass analyser. An electrode of the orthogonal acceleration Time of Flight mass analyser is preferably energised after a delay time after ions are released from the ion guide. The delay time is preferably progressively increased, decreased or varied. The delay time may be increased or decreased substantially linearly, in a regular manner or according to a predetermined manner.
According to another aspect of the present invention there is provided a method of mass spectrometry comprising:
temporally or spatially dispersing a group of ions according to a physico-chemical property;
receiving at least some of the ions which have become dispersed according to the physico-chemical property in an ion guide comprising a plurality of electrodes;
generating or creating multiple trapping regions along at least a portion of the length of the ion guide wherein at least a first group of ions having a physico-chemical property within a first range are trapped within a first trapping region and a second group of ions having a physico-chemical property within a second different range are trapped within a second different trapping region; and
translating the multiple trapping regions along at least a portion of the length of the ion guide.
According to another aspect of the present invention there is provided a method of mass spectrometry comprising:
releasing a first group ions having mass to charge ratios within a first range from a mass to charge ratio selective ion trap;
receiving at least some of the ions of the first group in an ion guide comprising a plurality of electrodes;
providing a first trapping region within the ion guide so that at least some of the ions of the first group are trapped within the first trapping region;
releasing a second group ions having mass to charge ratios within a second range from the mass selective ion trap;
receiving at least some of the ions of the second group in the ion guide;
providing a second different trapping region within the ion guide so that at least some of the ions of the second group are trapped within the second trapping region; and
translating at least the first and second trapping regions along at least a portion of the length of the ion guide.
According to another aspect of the present invention there is provided a mass spectrometer comprising:
a pulsed ion source for emitting a pulse of ions;
a region wherein ions in a pulse become dispersed according to their mass to charge ratio; and
an ion guide comprising a plurality of electrodes, wherein in use a plurality of trapping regions are generated or created along at least a portion of the length of the ion guide and wherein the ion guide is arranged to receive the ions which have become dispersed according to their mass to charge ratio so that at least 50%, 60%, 70%, 80%, 90% or 95% of the ions within a trapping region have substantially the same or similar mass to charge ratios.
Preferably, the plurality of trapping regions are translated along at least a portion of the length of the ion guide with a velocity which becomes progressively slower.
Preferably, bunches of ions emerge in use from the ion guide and the mass spectrometer further comprises an orthogonal acceleration Time of Flight mass analyser comprising an electrode for injecting ions into a drift region, wherein the electrode is energised after a delay period after each bunch of ions is released from a trapping region in the ion guide and wherein the energisation of the electrode is synchronised with the arrival of each bunch of ions at the electrode and wherein the delay period is progressively increased.
According to another aspect of the present invention there is provided a method of mass spectrometry comprising:
emitting a pulse of ions;
arranging for the ions in a pulse to become dispersed according to their mass to charge ratio;
providing an ion guide comprising a plurality of electrodes;
generating or creating a plurality of trapping regions along at least a portion of the length of the ion guide; and
receiving within the ion guide the ions which have become dispersed according to their mass to charge ratio so that at least 50%, 60%, 70%, 80%, 90% or 95% of the ions within a trapping region have substantially the same or similar mass to charge ratios.
The method preferably further comprises translating the plurality of trapping regions along at least a portion of the length of the ion guide with a velocity which becomes progressively slower.
Preferably, the method further comprises:
arranging for bunches of ions to emerge from the ion guide;
providing an orthogonal acceleration Time of Flight mass analyser comprising an electrode for injecting ions into a drift region;
energising the electrode after a delay period after each bunch of ions is released from a trapping region in the ion guide and in a synchronised manner with the arrival of each bunch of ions at the electrode; and
progressively increasing said delay period.
According to a particularly preferred embodiment a pulse of ions may be emitted from a pulsed ion source or released from an ion trap and then accelerated so that substantially all the ions have substantially the same energy. The ions may then be allowed to pass through a field free drift region which is maintained at a relatively low pressure so that ions of different mass to charge ratios will travel through the drift region with different velocities. Accordingly, ions having a relatively low mass to charge ratio will travel faster than ions having relatively higher mass to charge ratios and hence will reach the end of the drift region before other ions. Ions will therefore become temporally dispersed according to their mass to charge ratio. Similarly, if ions enter a drift region maintained at a relatively high pressure with an axial electric field to urge ions through the drift region then the ions will become temporally dispersed according to their ion mobility.
An advantage of the preferred embodiment is that once ions have been dispersed according to a physico-chemical property such as ion mobility or mass to charge ratio, then ions having substantially the same or similar physico-chemical properties can be trapped and stored within the same trapping region within the ion guide. The trapping regions are then translated along the ion guide so that the next fraction of ions arriving at the ion guide is received within the next trapping region.
The preferred embodiment allows ions having substantially similar properties to be ejected from the ion guide at substantially the same time. This is particularly useful and enables, for example, the delay time of a pusher/puller electrode of a Time of Flight mass analyser downstream of the ion guide to be set so that substantially all the ions released from the ion guide in a packet of ions are then orthogonally accelerated into the drift region of the mass analyser.
According to an embodiment, as groups of ions having larger mass to charge ratios become trapped within separate trapping regions within the ion guide, then the trapping regions towards the exit of the ion guide will contain ions having relatively lower mass to charge ratios whereas the trapping regions towards the entrance of the ion guide will contain ions having relatively higher mass to charge ratios. Each packet of ions released from the exit of the ion guide will therefore have an average mass to charge ratio which is slightly higher than that of a preceding package of ions released from the ion guide.
The preferred embodiment is particularly useful when a discontinuous mass analyser such as a quadrupole ion trap, FTICR mass analyser or Time of Flight mass analyser is used. Discontinuous mass analysers operate by receiving a packet of ions which have been accelerated to a given energy. However, this causes ions with different mass to charge ratios to travel with different velocities to the mass analyser. Accordingly, if the packet of ions being passed to the mass analyser has a wide range of mass to charge ratios then different ions will arrive at the mass analyser at different times. In some circumstances this makes it difficult or even impossible to analyse all the different ions and hence this can result in a relatively low duty cycle and accordingly low sensitivity. For example, if the mass analyser is an orthogonal acceleration Time of Flight mass analyser then only ions in the acceleration region at the time of the acceleration pulse will be accelerated into the Time of Flight analyser and the other ions arriving at the pusher electrode before or after the acceleration pulse will be lost.
A particular advantage of the preferred embodiment is that it can be ensured that only ions with a relatively narrow range of mass to charge ratios exit the ion guide at any given time. This allows the delay time of the orthogonal acceleration pulse to be effectively synchronised with the arrival of those ions at the acceleration region. In this way the sampling duty cycle for these ions can be as high as 100% and hence the sensitivity of the mass spectrometer can be very high.
The next packet of ions to be released from the ion guide will also preferably have a narrow spread of mass to charge ratios. The average mass to charge ratio of the ions in this packet will be slightly higher than the previous packet of ions and hence the delay time of the orthogonal acceleration pulse can be substantially synchronised with the arrival of those ions at the acceleration region.
The separation of ions according to mass to charge ratio before arrival at the preferred ion guide may take place in a field free region and/or in an ion guide. If an ion guide is used then the ion guide is preferably an RF ion guide. However, according to less preferred embodiments other types of ion guides such as guide wire ion guides may be used.
According to a preferred embodiment ions may be generated from a pulsed ion source e.g. a laser ablation or MALDI ion source or alternatively the ions may be released in a pulse from an ion trap. Ions then preferably travel through a field free flight tube to the preferred ion guide which is provided with a plurality of trapping regions which are translated along the length of the ion guide. The trapping regions may be created by applying transient DC voltages to certain electrodes so that potential wells are formed between these electrodes. The transient DC voltages are then progressively applied to subsequent electrodes so that the trapping regions move along the ion guide which may be referred to hereinafter as a xe2x80x9ctravelling wave ion guidexe2x80x9d.
The ions once released from the ion guide may then be passed through a second field free flight tube to an orthogonal acceleration Time of Flight mass analyser The field free flight tubes are preferably maintained at relatively low pressures e.g.  less than 0.0001 mbar whereas the ion guide with multiple trapping regions is preferably maintained at an intermediate pressure e.g. between 0.001 and 10 mbar.
In the following the distance in meters from the pulsed ion source or ion trap to the entrance of the travelling wave ion guide is L1, the length of the travelling wave ion guide is L2 and the distance from the exit of the travelling wave ion guide to the centre of an orthogonal acceleration Time of Flight acceleration region is L3. The ions are preferably accelerated through a voltage difference of V1 at the ion source or ion trap so that they have energy E1 of zeV1 electron volts. Accordingly, for ions having a mass m the arrival time T1 (in xcexcs) of ions at the entrance to the travelling wave ion guide after they have been ejected from the ion source or emitted from an upstream ion trap is given by;       T    1    =      72    ⁢          L      1        ⁢                  m                  zeV          1                    
The velocity v of these ions will be:   v  =            L      1              T      1      
The travelling wave ion guide is preferably maintained at a pressure between 0.0001 and 100 mbar, further preferably between 0.001 and 10 mbar. At these pressures the gas density is sufficient to impose a viscous drag on the ions and hence the gas will appear as a viscous medium to the ions and will act to slow the ions.
It is preferably arranged that the velocity vwave of one or more transient DC voltages or one or more transient DC voltage waveforms progressively applied to the electrodes forming the ion guide is equal to the velocity v of the ions as they arrive at the entrance to the travelling wave ion guide Since the velocity of the ions arriving at the entrance to the ion guide is inversely proportional to elapsed time T1 from release of ions from the ion source or ion trap, then the velocity vwave of the travelling wave is preferably arranged to decrease with time in a similar manner.
Since the travelling wave velocity vwave is equal to xcex/T where xcex is the wavelength and T is the cycle time of the travelling DC waveform, then it follows that the cycle time T should vary in proportion to the elapsed time T1. In other words, for the travelling wave velocity to always equal the velocity of the ions arriving at the entrance to the preferred ion guide, the wave cycle time T should preferably increase linearly with time.
Since the travelling DC wave velocity vwave preferably continuously slows, it could be considered that the ions might travel on ahead of the travelling DC wave. However, the viscous drag resulting from frequent collisions with gas molecules prevents the ions from building up excessive velocity. Consequently, the ions tend to ride on the travelling DC wave rather than run ahead of the travelling DC wave and execute excessive oscillations within the travelling potential wells.
If, in time xcex4t, the ions travel distance xcex4l within the ion guide:
xcex4l=vxcex4t 
then if the time at which the ions exit the travelling wave ion guide is T2 then the distance xcex94L travelled within the ion guide is:                               Δ          ⁢                      xe2x80x83                    ⁢          L                =                              ∫                          T              1                                      T              2                                ⁢                      v            ⁢                          xe2x80x83                        ⁢            δ            ⁢                          xe2x80x83                        ⁢            t                                                            Δ          ⁢                      xe2x80x83                    ⁢          L                =                              ∫                          T              1                                      T              2                                ⁢                                                    L                1                            t                        ⁢            δ            ⁢                          xe2x80x83                        ⁢            t                                                            Δ          ⁢                      xe2x80x83                    ⁢          L                =                              L            1                    ⁡                      (                                          ln                ⁡                                  (                                      T                    2                                    )                                            -                              ln                ⁡                                  (                                      T                    1                                    )                                                      )                                                            Δ          ⁢                      xe2x80x83                    ⁢          L                =                              L            1                    ⁢                      ln            ⁡                          (                                                T                  2                                                  T                  1                                            )                                          
Since the length of the ion guide is L2 and hence xcex94L=L2 then:                               L          2                =                              L            1                    ⁢                      ln            ⁡                          (                                                T                  2                                                  T                  1                                            )                                                                        T          2                =                              T            1                    ⁢                      ⅇ                          (                                                L                  2                                                  L                  1                                            )                                          
Hence, the velocity of the ions vx as they exit the travelling wave ion guide is equal to that of the travelling DC wave at the time of exit and therefore is:                               v          x                =                              L            1                                T            2                                                            v          x                =                                            L              1                                      T              1                                ⁢                      ⅇ                          -                              (                                                      L                    2                                                        L                    1                                                  )                                                                                      v          x                =                  v          ⁢                      xe2x80x83                    ⁢                      ⅇ                          -                              (                                                      L                    2                                                        L                    1                                                  )                                                        
Since the energy E1 of the ions at the entrance to the ion guide is:
E1=zeV1 
then since:   E  =            1      2        ⁢          mv      2      
if the energy of the ions at the exit of the travelling wave ion guide is E2 then:                               E          2                =                              1            2                    ⁢                      mv            x            2                                                            E          2                =                              1            2                    ⁢                      mv            2                    ⁢                      ⅇ                                          -                2                            ⁢                              (                                                      L                    2                                                        L                    1                                                  )                                                                                      E          2                =                              E            1                    ⁢                      ⅇ                                          -                2                            ⁢                              (                                                      L                    2                                                        L                    1                                                  )                                                        
Hence, the energy E2 of the ions as they exit the travelling wave ion guide is a constant fraction equal to exp (xe2x88x922(L2/L1)) of the energy E1 they had on entering the ion guide. Hence their energy is independent of their mass to charge ratio. For two reasons this is a particularly favourable outcome.
Firstly, the gas in the travelling wave ion guide will result in frequent ion-molecule collisions which in turn will cause the ions to lose kinetic energy. In the presence of an RF confining field both the axial and radial kinetic energies will be reduced. Furthermore, the axial and radial energies decay approximately exponentially with distance travelled into the ion guide as disclosed in J. Am. Soc. Mass Spectrom., 1998, 9, pp 569-579. From computer simulations it has been estimated that the kinetic energies in the axial and radial directions reduce to 10% whilst passing through a nitrogen gas pressure-distance product of approximately 0.1 mbar-cm. Hence, both the travelling wave velocity and the ion kinetic energies preferably decay exponentially. These two exponential decay rates can be arranged to be approximately the same by appropriate choice of the collision gas molecular mass and pressure. If the travelling wave velocity were set significantly higher than the intrinsic velocity of the ions, then the ions may be caused to fragment which may be undesirable in some modes of operation.
Secondly, it is a characteristic of orthogonal acceleration Time of Flight mass spectrometers that all ions, irrespective of their mass to charge ratio, need to be injected into the orthogonal acceleration region with substantially the same axial energy. Since the ions exiting the travelling wave ion guide will have substantially constant energy independent of their mass to charge ratio then it is only necessary to accelerate the ions through a constant voltage difference V3 after they have left the travelling wave ion guide to give the ions the correct energy E3=E2+zeV3 when injected into the orthogonal acceleration region of the orthogonal Time of Flight mass analyser.
As the ions exit the travelling wave ion guide in pulses they will be grouped such that each group contains only ions within a limited range of mass to charge ratios and each group of ions will have ions with an average mass to charge ratio slightly higher than that of a preceding group emitted from the ion guide. Each group of ions after the acceleration stage will have substantially the same energy E3 and therefore their substantially similar transit time to the orthogonal acceleration region of the orthogonal acceleration Time of Flight mass analyser will be proportional to the square root of their average mass. If for each group of ions exiting the travelling wave ion guide the delay time Tx of the pusher electrode of the orthogonal acceleration Time of Flight mass analyser is increased in proportion to the square root of the mass of ions released from the ion guide, then the orthogonal acceleration can be arranged to coincide with the arrival of each group of ions at the orthogonal acceleration region. A very high (approximately 100%) duty cycle can therefore be achieved according to the preferred embodiment.
The time for ions to travel to the exit of the ion guide is T2 which is proportional to T1 which is in turn proportional to the square root of the mass to charge ratio of the ions:                               T          2                =                              T            1                    ⁢                      ⅇ                          (                                                L                  2                                                  L                  1                                            )                                                                        T          1                =                  72          ⁢                      xe2x80x83                    ⁢                      L            1                    ⁢                                    m                              E                1                                                        
The time for ions to travel from the exit of the travelling wave ion guide to the orthogonal acceleration region is the delay time Tx and is also proportional to the square root of the mass to charge ratio of the ions:       T    x    =      72    ⁢          xe2x80x83        ⁢          L      3        ⁢                  m                  E          3                    
Hence the delay time Tx needs to be proportional to T1:       T    x    =                    L        3                    L        1              ⁢                            E          1                          E          3                      ⁢          T      1      
In other words, the delay time Tx needs to increase linearly with the time from the original pulse of ions leaving the ion source or ion trap.
As a consequence of the gas present in the travelling wave ion guide and preferably the continuously slowing travelling DC wave velocity, the kinetic energy of the ions will be reduced by a constant factor equal to exp (xe2x88x922(L2/L1)) when they emerge from the travelling wave ion guide. If the ions have a substantial energy spread when they enter the travelling wave ion guide then advantageously this will be reduced.
In summary, both the travelling waveform cycle time and the pusher electrode delay time may increase substantially linearly with time starting from the time of the original pulse of ions leaving the pulsed ion source or ion trap. Ions will exit from the travelling wave ion guide with reduced energy and reduced energy spread. The ions exiting the ion guide will also have a substantially constant energy and may be accelerated to higher constant energy with a constant difference in potential. Under such circumstances, ions will arrive at the orthogonal acceleration stage of the orthogonal Time of Flight mass analyser with substantially constant energy and the sampling duty cycle may be as high as 100% for all ions irrespective of their mass.
According to a second main embodiment instead of using a pulsed ion source and a flight tube, a mass to charge ratio selective ion trap such as a 3D (xe2x80x9cPaulxe2x80x9d) or 2D (linear) quadrupole ion trap may be used. The mass to charge ratio selective ion trap is preferably operated in a mass selective ejection mode or resonance ejection mode. For such an ion trap, in which only ions having a relatively narrow range of mass to charge ratios are released from the ion trap, the initial flight tube previously required to separate ions according to their mass to charge ratios is no longer required. Hence, the ion trap may now be positioned in close proximity or directly adjacent to the entrance to the travelling wave ion guide.
The operation of the travelling wave ion guide may be substantially the same as that previously described in relation to the first embodiment. The velocity of the travelling wave may be arranged to be programmed as though the ions of the selected masses had originated from the ion source or ion trap according to the first main embodiment. Hence, the travelling wave ion guide may be arranged to be co-ordinated with the mass to charge ratios of the ions ejected from the ion trap at any particular point in time. Since the travelling DC potential wave is programmed as though the ions originated from a virtual ion source, the programming of the travelling wave ion guide can be selected for any virtual flight tube length L1. This now provides a degree of freedom in the choice of exponential decay of ion energies as they travel through the travelling wave ion guide. This degree of freedom is in addition to that of the gas molecular weight and gas pressure that determines the exponential decay rate of the ion kinetic energies due to ion-molecule collisions. Hence, this arrangement provides greater flexibility when seeking to match these two decay rates.
Any energy spread in the ion beam ejected from the mass to charge ratio selective ion trap may also be reduced as the ions travel through the travelling wave ion guide. The addition of the travelling wave ion guide and flight tube between the ion trap and orthogonal acceleration Time of Flight mass analyser reduce the energy spread of the ions and hence improves the sensitivity and resolution of the Time of Flight mass spectrometer.
The preferred embodiment entails superimposing a repeating pattern of DC electrical potentials along the length of the ion guide so as to form a periodic DC potential waveform (xe2x80x9ctravelling wavexe2x80x9d) and causing the waveform to travel or the applied DC potentials to be translated along the ion guide in the direction in which it is required to move the ions and at a velocity at which it is required to move the ions.
The AC or RF ion guide may comprise a multipole rod set or stacked ring set. The ion guide is preferably segmented in the axial direction so that independent transient DC potentials may be applied to each segment and superimposed on top of an AC or RF confining voltage and any constant DC offset voltage. The DC potentials are changed temporally to generate a travelling DC wave in the axial direction.
At any instant in time a voltage gradient is generated between segments to push or pull the ions in a certain direction. As the voltage gradient moves in the required direction so do the ions. The individual DC voltages on each of the segments are preferably programmed to create the desired waveform. The individual DC voltages on each of the segments may also be programmed to change in synchronism such that the waveform (and preferably the wavelength) is maintained but shifted in the direction in which it is desired to move the ions.
The DC potential waveform is preferably superimposed on any nominally imposed axial DC voltage offset. No axial voltage gradient is required although less preferably the travelling DC wave may be provided in conjunction with an axial DC voltage gradient by the application of the travelling waveform superimposed on any axial DC voltage gradient. The transient DC voltage applied to each segment may be above or below that of the constant DC voltage offset to cause movement of the ions in the axial direction or could be a combination of both.